The aim of this research is to understand how the stability of an alpha-helix influences the pathway and kinetics of protein folding. Apamin, a small bee venom protein which forms an alpha-helix on the C-terminal end and contains two disulfide bonds, will be used as the model system. The mechanism for folding from the unfolded state of apamin, with reduced thiols, to the native folded state, with two disulfide bonds, will be studied by trapping the disulfide intermediates with iodoacetic acid throughout the folding process. Separation of the intermediates by HPLC will determine the rates acid throughout the folding processes. Separation of the intermediates by HPLC will determine the rates of build-up and decay of each intermediate, while enzymatic cleavage, followed by separation of the fragments, will tell which cysteines are linked by disulfide bonds. In order to study the stability of the alpha-helix in apamin, the C- terminal helical part of apamin will be synthesized by solid phase peptide methods, replacing the cysteines by alanines to avoid disulfide bond formation. The stability will be studied by using the helix-stabilizing properties of trifluoroethanol. Alpha-Helix formation will be studied by circular dichroism, to measure overall helicity, and by two-dimensional NMR, to monitor the helical transition of each amino acid. After understanding the folding of natural apamin and the stability of its helix, apamin derivatives with substitutions on the C-terminal helix will be synthesized. Comparisons of the folding kinetics and helical stability of the derivatives with natural apamin will provide information about the relationship between alpha-helix stability and folding kinetics. This research will provide new insight into how the stability of an alpha-helix influences the folding of small proteins.